Short and Long term Cardiovascular Effects of Maternal Preeclampsia

Katharine Stanley Consultant Obstetrician

Norfolk and Norwich University Hospital England

3rd International Congress on Cardiac Problems in Pregnancy

Venice February 2014

What is preeclampsia ? • Defined as the onset of hypertension ( >150/ 90 mm Hg + proteinuria ( > 300 mg/

24 hours) after 20 weeks gestation – 3-5% pregnancies, 16% recur

• Multisystem involvement:

– CNS: eclampsia, stroke, cerebral oedema , retinal detachment – Renal: cortical necrosis, tubular necrosis, acute renal failure – Hepatic : HELLP, hepatic rupture – Coagulation: DIC, microangiopathic haemolysis, HELLP – Respiratory: laryngeal oedema, pulmonary oedema – Placental: infarction, abruption , IUGR , IUFD

• Maternal Mortality / Morbidity

– 0.83/100,000, no change over 25 years – 50% from stroke – Eclampsia27/10,000 – 2.3% CVA rate , 3.1% fatality – Pulmonary oedema 2.3%

• 30% of women with pre-existing heart disease who develop PET develop heart failure

• OR for development of heart failure if develop PET is 7.1

Pathophysiology of PET

Lack of remodelling of spiral arteries, responsible for delivery of oxygenated

blood to intervillous space

8-18 weeks

Placental ischaemia

Production of placental factors

Endothelial dysfunction

Reduced perfusion of maternal and fetal end organs

Clinical manifestation of disease

Cardiac function in normal pregnancy

Reminder for Obstetricians

Cardiac output

Stroke Volume

Heart Rate

CO = Stroke Volume x Heart Rate

Mean Arterial Pressure Cardiac Output x 80

TPVR=

Modified from Robson, Am J Physiology 1989

Cardiac Remodelling for Obstetricians

Eccentric hypertrophy: Increased LV mass, No change in ratio of wall thickness to cavity dimensions Normal Contractility Response to increased volume load /athletes

Concentric hypertrophy, Increased LV mass, increased ratio wall thickness to cavity dimensions. Less compliance, hence diastolic dysfunction. Response to increased afterload / hypertension

Normal

Cardiac remodelling in normal pregnancy

Normal Pregnancy : Eccentric hypertrophy: No significant change in ratio of wall thickness to cavity dimensions. 11%- 25% increase LV thickness, 23% LV mass increase, Response to increased circulating volume i.e. preload No change in contractility

Normal , non pregnant

Haemodynamic changes in Preeclampsia

• Literature contradictory

• Relationship to treatment -prior to onset of treatment i.e. mild cases

• Technological restrictions e.g. 2D speckle study shown -myocardial dysfunction not otherwise apparent

• Recognition of spectrum of disease, e.g. mainly term births, some IUGR,

• Possibility of progression of disease, or heterogeneity of disease.

• Some longitudinal studies, before onset of clinically apparent disease

Prior to disease

At time of disease

Mean Blood pressure

Increased or unchanged

Increased

Cardiac Output

Reduced or Increased

Reduced or unchanged

Systemic vascular resistance

Increased or unchanged or reduced

Increased

Early v late disease

• Clinically different

• Aggressive, earlier

• Abnormal Uterine artery doppler + IUGR

• Increased morbidity

• ? Different aetiology

• Different haemodynamics

Early pregnancy

At time of disease

Cardiac Output (Index)

Increased Reduced 2.6 v 3.2 l/min/m² p=0.0001

Systemic vascular resistance

Increased 1129 v 852 dyne/s/cm³ p<0.05

Stroke Volume (Index)

Reduced 33 v 40 ml/m² p = 0.001

Diastolic function Reduced

Systolic function Reduced

Melchiorre et al ,Hypertension in pregnancy 2012 31(4) 454-471 Valensise et al Hypertension 2008 52 873-880

Khaw et al BJOG 2008 Sep et al BJOG 2011 Bosio Obstet Gynecol 1999

Cardiac geometry in PET

Normal Pregnancy: Eccentric hypertrophy: 11%- 25% increase LV thickness, 23% LV mass increase, No significant change in ratio of wall thickness to cavity dimensions. Response to preload, i.e. increased circulating volume

PET: Concentric hypertrophy, Similar LV dimensions to normal pregnancy, Increased LV mass, increased ratio wall thickness to cavity dimensions. Less compliance, hence diastolic dysfunction+/- systolic dysfunction. Response to Increased afterload (SVR)

Non Pregnant Heart

Preclinical disease , high risk women

• 1345 women, 24 weeks

• 32 Late PET

• 75 early PET

Normal pregnancy

Early PET

Late PET

CO L/min

6.61 4.49 8.96

TVR Dyne/s/cm

990 1605 739

LV diastolic diameter

4.85 4.51 5.16

Valensise Hypertension 2008

Comparison of cardiac dysfunction in term and preterm PET at time of disease

Melchiorre et al, Hypertension in pregnancy 2012

Early pregnancy

Hyperdynamic,

High CO

Low / Normal TVR

Mild disease

Late onset , No IUGR

Remains hyperdynamic, High TVR, Less remodelling,

Resolves post partum

Severe disease

Early Onset/ IUGR

Hypodynamic

Low CO, High TVR

Diastolic dysfunction,

Concentric Hypertrophy

Persists postpartum

Early pregnancy

Hyperdynamic,

High CO

Low / Normal TVR

Mild disease

?Late onset , No IUGR

Remains hyperdynamic, High TVR, Eccentric remodelling,

Resolves post partum

Severe disease

?Early Onset/ IUGR

Hypodynamic

Low CO, High TVR

Diastolic dysfunction,

Concentric Hypertrophy

Persists postpartum

Early pregnancy

Hyperdynamic,

High CO

Low / Normal TVR

Mild disease

?Late onset , No IUGR

Remains hyperdynamic, High TVR,

Eccentric remodelling, Resolves post partum

Severe disease

?Early Onset/ IUGR

Hypodynamic

Low CO, High TVR

Diastolic dysfunction,

Concentric Hypertrophy

Persists postpartum

Early pregnancy

Hyperdynamic,

High CO

Low / Normal TVR

Mild disease

?Late onset , No IUGR

Remains hyperdynamic, High TVR,

Eccentric remodelling, Resolves post partum

Severe disease

?Early Onset/ IUGR

Hypodynamic

Low CO, High TVR

Diastolic dysfunction,

Concentric Hypertrophy

Persists postpartum

Early pregnancy

Hyperdynamic,

High CO

Low / Normal TVR

Mild disease

?Late onset , No IUGR

Remains hyperdynamic, High TVR,

Eccentric remodelling, Resolves post partum

Severe disease

?Early Onset/ IUGR

Hypodynamic

Low CO, High TVR

Diastolic dysfunction,

Concentric Hypertrophy

Persists postpartum

Preterm PET

Term PET Controls P

Biventricular systolic dysfunction

26% 4% <0.05

Severe left ventricular hypertrophy

19% 2% 0 <0.05

Stage B asymptomatic heart failure at 1 year

70% 24% 19% <0.001

Hypertension at 2 years

77% 13.5% 1.3%

Changes Persist Postnatally Term v Preterm Preeclampsia

Melchiorre et al 2011, Current opinion in Obstetrics and Gynaecology

Long term maternal effects of PET

• PET increases the lifetime risk of cardiovascular disease

• Preterm PET increases this risk further

PET and risk of IHD in later life: RR 3.7 (2.70 – 5.05) n = 20,000

Severity of PET , and risk of IHD

Bellamy et al BMJ 2007 335:974

Conclusion

• Preeclampsia is associated, at the time of severe disease , with a hypodynamic circulation including Low CO , high TVR, concentric remodelling and diastolic dysfunction

• These changes are preceded by a hyperdynamic preclinical stage,

• The dysfunction persists postpartum, particularly early onset disease

• Women with pre-existing heart disease may not tolerate these changes, hence the 30% risk of heart failure if PET develops

• PET, particularly preterm PET, identifies women at risk of IHD, who may be suitable for therapeutic intervention.

Thank you